
The progression of Alzheimer's disease could be better predicted by imaging microglial activation levels using positron emission tomography (PET) than with beta-amyloid PET imaging, reveals new research published in the Journal of Nuclear Medicine.
According to the Alzheimer's Association, an estimated 5.3 million Americans are currently living with Alzheimer's disease. By 2025, that number is expected to increase to more than seven million. The hallmark brain changes for those with Alzheimer's disease include the accumulation of beta-amyloid plaques. When microglial cells from the central nervous system recognize the presence of beta-amyloid plaques, they produce an inflammatory reaction in the brain.
"The 18-kD translocator protein (TSPO) is highly expressed in activated microglia, which makes it a valuable biomarker to assess inflammation in the brain," said Matthias Brendel, MD, MHBA, at Ludwig-Maximilians-University of Munich in Germany. "In our study, we utilized TSPO-PET imaging to determine whether microglial activation had any influence on cognitive outcomes in an amyloid mouse model."
Transgenic mice with the highest TSPO PET signal in the forebrain or other areas associated with spatial learning tended to have better cognitive performance in the water maze, while beta-amyloid signals in the same areas of the brain showed no correlation to cognitive outcomes in the maze. Researchers found that an earlier microglial response to amyloid pathology in transgenic mice also protected synaptic density at follow-up. Specifically, transgenic mice with higher TSPO expression at eight months had much better cognitive outcomes in the water maze and higher synaptic density as confirmed by immunochemistry analyses.
"This study provides the first evidence that the level of microglial activation could be a far better predictor of current and future cognitive performance than beta-amyloid levels," noted Brendel. "Keeping the limitations of mouse models in mind, it could be crucial to modify an individual's microglial activation state to ameliorate future cognitive decline. We believe that a balanced microglia activation is crucial for prevention of cognitive impairment."
Source: Eurekalert
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